1. Field of the Invention
The present invention relates to methods of passive and active dynamic infrared imaging of a tumor or lesion (“DIRI”) that heats or cools the tumor or lesion. Patterns of intensity of infrared emission in the infrared image are related to the level of vascularity or metabolic activity of the tumor or lesion, and are used to identify the size and shape of the tumor or lesion. Changes in the patterns of infrared emission determined by comparing images taken before, during and after the onset of drug or radiation therapy, are used to assess the efficacy of the therapy. The methods can also be used to study tissue that has been affected by angiogenic diseases.
2. Description of the Related Art
Tumor angiogenesis, the recruitment of new blood vessels by a growing tumor from existing neighboring vessels, is essential for the growth and persistence of solid tumors and their metastases (Folkman, 1989; Hori et al., 1991; Kim et al., 1993; Millauer et al., 1994). This recruitment of new microvasculature is a central process in tumor growth and aggressive spreading of the tumor through hematogenous metastasis. Angiogenesis depends upon the production of angiogenic factors by host or tumor cells, or both. All solid tumors require angiogenesis for growth and metastasis. Tumors greater than 2 millimeters in size, must obtain their own blood supply; this is accomplished by inducing the growth of new capillary blood vessels. Once these new blood vessels become embedded in the tumor, they provide a means for tumor cells to enter the circulation and metastasize to distant sites such as liver, lung or bone (Weidner, N., et al., The New England Journal of Medicine, 324(1), 1-8 (1991). The level of angiogenesis is thought to be an important parameter for the staging of tumors, and new therapies are being developed which attack the process of angiogenesis for the purpose of attempting to control tumor growth and tumor spread by restricting or eliminating the tumor blood supply. It is therefore of clinical importance to be able to monitor angiogenesis in tumors in a noninvasive manner.
Although angiogenesis is a highly regulated process under normal conditions, many diseases (characterized as angiogenic diseases) are driven by persistent unregulated angiogenesis. Unregulated angiogenesis may either cause a particular disease directly or exacerbate an existing pathological condition. For example, ocular neovacularization has been implicated as the most common cause of blindness and dominates approximately 20 eye diseases. In certain existing conditions, such as arthritis, newly formed capillary blood vessels invade the joints and destroy cartilage. In diabetes, new capillaries formed in the retina invade the vitreous, bleed, and cause blindness. Growth and metastasis of solid tumors are also dependent on angiogenesis (Folkman, J., Cancer Research, 46, 467-473 (1986), Folkman, J., Journal of the National Cancer Institute, 82, 4-6. (1989).
At present there is no single imaging method capable of providing quantitative characterization of tumor angiogenesis (Passe, et al., Radiology 203:593-600, 1997) or other abnormal angiogenesis. Such a method would facilitate monitoring the efficacy of antiangiogenesis factors for therapeutic use, tumor staging, and diagnosis of angiogenic diseases.